Most intermediate size natural and synthetic peptides are amorphous substances. Many of them have pharmacologically interesting properties, such as many nona- and decapeptides which are LHRH (luteinizing hormone-releasing hormone) antagonists. One particular substance of this kind known only in amorphous form is the synthetic decapeptide of the formula (I)Ac-D-2Nal-D-4ClPhe-D-3Pal-Ser-MeTyr-D-Asn-Leu-Lye(iPr)-Pro-D-Ala-NH2   (I)
which, being a potent LHRH antagonist, has desirable pharmacological properties.
For use in pharmaceutical preparations it is necessary for the LHRH antagonist (I) and nona- and decapeptides of similar structure to be essentially pure. The raw product obtained in the last step of a multiple-step synthesis is purified by chromatographic and other methods. To eliminate residual solvent from the chromatography a thus purified product usually has to be dissolved in an aqueous medium and freeze-dried. This is a costly process producing a voluminous product which is not easy to handle.
A process of purification of an otherwise pure peptide from residual organic solvent by other means than freeze-drying thus is desirable.
WO 0018423 A discloses the use of the combination of cyclodextrin and a LHBR peptide analogue, including its pharmaceutically acceptable salts, for the preparation of a pharmaceutical composition for oral administration. Abarelix is a preferred LHRM analogue. Acetate salts of the LHRH peptide antagoniste of D1 are disclosed to be pharmaceutically acceptable in general. The compounds of WO 0018423 are useful in the manufacture of medicaments.
WO 0055190 A discloses decapeptide LHRM antagonists for the manufacture of medicaments against hormone dependent tumors and hormone influenced diseases, which may be purified by preparative HPLC, and freeze dried.
EP 0955308 A discloses a process for the transformation or hydrochloride salts of decapeptide LHRH antagonists to their diacetate salts in a concurrent single-step purification by liquid chromatography.